1.Financial Benefits of Renal Dose-Adjusted Dipeptidyl Peptidase-4 Inhibitors for Patients with Type 2 Diabetes and Chronic Kidney Disease
Hun Jee CHOE ; Yeh-Hee KO ; Sun Joon MOON ; Chang Ho AHN ; Kyoung Hwa HA ; Hyeongsuk LEE ; Jae Hyun BAE ; Hyung Joon JOO ; Hyejin LEE ; Jang Wook SON ; Dae Jung KIM ; Sin Gon KIM ; Kwangsoo KIM ; Young Min CHO
Endocrinology and Metabolism 2024;39(4):622-631
Background:
Dipeptidyl peptidase-4 (DPP4) inhibitors are frequently prescribed for patients with type 2 diabetes; however, their cost can pose a significant barrier for those with impaired kidney function. This study aimed to estimate the economic benefits of substituting non-renal dose-adjusted (NRDA) DPP4 inhibitors with renal dose-adjusted (RDA) DPP4 inhibitors in patients with both impaired kidney function and type 2 diabetes.
Methods:
This retrospective cohort study was conducted from January 1, 2012 to December 31, 2018, using data obtained from common data models of five medical centers in Korea. Model 1 applied the prescription pattern of participants with preserved kidney function to those with impaired kidney function. In contrast, model 2 replaced all NRDA DPP4 inhibitors with RDA DPP4 inhibitors, adjusting the doses of RDA DPP4 inhibitors based on individual kidney function. The primary outcome was the cost difference between the two models.
Results:
In total, 67,964,996 prescription records were analyzed. NRDA DPP4 inhibitors were more frequently prescribed to patients with impaired kidney function than in those with preserved kidney function (25.7%, 51.3%, 64.3%, and 71.6% in patients with estimated glomerular filtration rates [eGFRs] of ≥60, <60, <45, and <30 mL/min/1.73 m2, respectively). When model 1 was applied, the cost savings per year were 7.6% for eGFR <60 mL/min/1.73 m2 and 30.4% for eGFR <30 mL/min/1.73 m2. According to model 2, 15.4% to 51.2% per year could be saved depending on kidney impairment severity.
Conclusion
Adjusting the doses of RDA DPP4 inhibitors based on individual kidney function could alleviate the economic burden associated with medical expenses.
2.Study Design and Protocol for a Randomized Controlled Trial to Assess Long-Term Efficacy and Safety of a Triple Combination of Ezetimibe, Fenofibrate, and Moderate-Intensity Statin in Patients with Type 2 Diabetes and Modifiable Cardiovascular Risk Factors (ENSEMBLE)
Nam Hoon KIM ; Juneyoung LEE ; Suk CHON ; Jae Myung YU ; In-Kyung JEONG ; Soo LIM ; Won Jun KIM ; Keeho SONG ; Ho Chan CHO ; Hea Min YU ; Kyoung-Ah KIM ; Sang Soo KIM ; Soon Hee LEE ; Chong Hwa KIM ; Soo Heon KWAK ; Yong‐ho LEE ; Choon Hee CHUNG ; Sihoon LEE ; Heung Yong JIN ; Jae Hyuk LEE ; Gwanpyo KOH ; Sang-Yong KIM ; Jaetaek KIM ; Ju Hee LEE ; Tae Nyun KIM ; Hyun Jeong JEON ; Ji Hyun LEE ; Jae-Han JEON ; Hye Jin YOO ; Hee Kyung KIM ; Hyeong-Kyu PARK ; Il Seong NAM-GOONG ; Seongbin HONG ; Chul Woo AHN ; Ji Hee YU ; Jong Heon PARK ; Keun-Gyu PARK ; Chan Ho PARK ; Kyong Hye JOUNG ; Ohk-Hyun RYU ; Keun Yong PARK ; Eun-Gyoung HONG ; Bong-Soo CHA ; Kyu Chang WON ; Yoon-Sok CHUNG ; Sin Gon KIM
Endocrinology and Metabolism 2024;39(5):722-731
Background:
Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined.
Methods:
This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months.
Conclusion
This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.
4.Olmesartan-associated Enteropathy with Acute Kidney Injury
Moo Jin KANG ; Kyung Hwa MIN ; Hyung Wook KIM ; Su Bum PARK ; Dae Hwan KANG ; Cheol Woong CHOI ; Su Jin KIM ; Hyeong Seok NAM ; Dae Gon RYU
The Korean Journal of Gastroenterology 2022;79(3):130-134
Olmesartan, a recently introduced angiotensin II receptor blocker for hypertension, has been reported to cause drug-induced small bowel enteropathy. The diagnosis of olmesartan-associated enteropathy (OAE) needs clinical suspicion and the exclusion of coeliac disease, as it mimics coeliac sprue. Once diagnosed, it can be completely cured with the discontinuation of olmesartan. However, due to the extremely low incidence of OAE in Korea, clinical suspicion and diagnosis may be a challenge. The authors report the first case of OAE presenting with chronic diarrhea and acute kidney injury in Korea.
5.Vertebral Artery Dissecting Aneurysm Causing Central Tapia’s Syndrome: A Case Report
Yong Woo SHIM ; Jung Hyun PARK ; Sung-Tae KIM ; Jin Wook BAEK ; Hyun Gon LEE ; Jung Hae KO ; Sung Hwa PAENG ; Se Young PYO ; Sung-Chul JIN ; Hae Woong JEONG ; Young Gyun JEONG
Neurointervention 2021;16(2):185-189
The central type of Tapia’s syndrome is an extremely rare presentation, characterized by unilateral paralysis of the vagal and hypoglossal nerves, contralateral hemiparesis, or hemihypesthesia. This report describes a case of a middle-aged patient who developed central Tapia’s syndrome due to a right vertebral artery dissecting aneurysm (VADA). The patient complained about swallowing difficulty and odynophagia. Right vocal cord paralysis, mild tongue deviation to the right side, left hypesthesia, and decreased temperature sensation with left hemiparesis were observed in neurologic exams. A right VADA and compression of the medulla oblongata due to the VADA were diagnosed on magnetic resonance imaging. Endovascular flow diversion of the right VADA was performed. After 1 year, all neurological symptoms and vocal cord paralysis were nearly resolved, but left hypesthesia remained with decreased nociception. We present and discuss how a VADA caused those symptoms and propose endovascular flow diversion as a treatment option.
6.Vertebral Artery Dissecting Aneurysm Causing Central Tapia’s Syndrome: A Case Report
Yong Woo SHIM ; Jung Hyun PARK ; Sung-Tae KIM ; Jin Wook BAEK ; Hyun Gon LEE ; Jung Hae KO ; Sung Hwa PAENG ; Se Young PYO ; Sung-Chul JIN ; Hae Woong JEONG ; Young Gyun JEONG
Neurointervention 2021;16(2):185-189
The central type of Tapia’s syndrome is an extremely rare presentation, characterized by unilateral paralysis of the vagal and hypoglossal nerves, contralateral hemiparesis, or hemihypesthesia. This report describes a case of a middle-aged patient who developed central Tapia’s syndrome due to a right vertebral artery dissecting aneurysm (VADA). The patient complained about swallowing difficulty and odynophagia. Right vocal cord paralysis, mild tongue deviation to the right side, left hypesthesia, and decreased temperature sensation with left hemiparesis were observed in neurologic exams. A right VADA and compression of the medulla oblongata due to the VADA were diagnosed on magnetic resonance imaging. Endovascular flow diversion of the right VADA was performed. After 1 year, all neurological symptoms and vocal cord paralysis were nearly resolved, but left hypesthesia remained with decreased nociception. We present and discuss how a VADA caused those symptoms and propose endovascular flow diversion as a treatment option.
7.Neuroimaging Findings in Patients with COVID-19: A Systematic Review and Meta-Analysis
Pyeong Hwa KIM ; Minjae KIM ; Chong Hyun SUH ; Sae Rom CHUNG ; Ji Eun PARK ; Soo Chin KIM ; Young Jun CHOI ; Jeong Hyun LEE ; Ho Sung KIM ; Jung Hwan BAEK ; Choong Gon CHOI ; Sang Joon KIM
Korean Journal of Radiology 2021;22(11):1875-1885
Objective:
Central nervous system involvement in coronavirus disease 2019 (COVID-19) has been increasingly reported. We performed a systematic review and meta-analysis to evaluate the incidence of radiologically demonstrated neurologic complications and detailed neuroimaging findings associated with COVID-19.
Materials and Methods:
A systematic literature search of MEDLINE/PubMed and EMBASE databases was performed up to September 17, 2020, and studies evaluating neuroimaging findings of COVID-19 using brain CT or MRI were included. Several cohort-based outcomes, including the proportion of patients with abnormal neuroimaging findings related to COVID-19 were evaluated. The proportion of patients showing specific neuroimaging findings was also assessed. Subgroup analyses were also conducted focusing on critically ill COVID-19 patients and results from studies that used MRI as the only imaging modality.
Results:
A total of 1394 COVID-19 patients who underwent neuroimaging from 17 studies were included; among them, 3.4% of the patients demonstrated COVID-19-related neuroimaging findings. Olfactory bulb abnormalities were the most commonly observed (23.1%). The predominant cerebral neuroimaging finding was white matter abnormality (17.6%), followed by acute/subacute ischemic infarction (16.0%), and encephalopathy (13.0%). Significantly more critically ill patients had COVID-19-related neuroimaging findings than other patients (9.1% vs. 1.6%; p = 0.029). The type of imaging modality used did not significantly affect the proportion of COVID-19-related neuroimaging findings.
Conclusion
Abnormal neuroimaging findings were occasionally observed in COVID-19 patients. Olfactory bulb abnormalities were the most commonly observed finding. Critically ill patients showed abnormal neuroimaging findings more frequently than the other patient groups. White matter abnormalities, ischemic infarctions, and encephalopathies were the common cerebral neuroimaging findings.
8.Rapid Cartilage Regeneration of Spheroids Composed of Human Nasal Septum-Derived Chondrocyte in Rat Osteochondral Defect Model
Jung Ho JEON ; Byeong Gon YUN ; Min Jae LIM ; Seok Jung KIM ; Mi Hyun LIM ; Jung Yeon LIM ; Sun Hwa PARK ; Sung Won KIM
Tissue Engineering and Regenerative Medicine 2020;17(1):81-90
Background:
Cell-based therapies have been studied for articular cartilage regeneration. Articular cartilage defects have little treatments because articular cartilage was limited regenerative capacity. Damaged articular cartilage is difficult to obtain a successful therapeutic effect. In additionally these articular cartilage defects often cause osteoarthritis. Chondrocyte implantation is a widely available therapy used for regeneration of articular cartilage because this tissue has poor repair capacity after injury. Human nasal septum-drived chondrocytes (hNCs) from the septum show greater proliferation ability and chondrogenic capacity than human articular chondrocytes (hACs), even across different donors with different ages. Moreover, the chondrogenic properties of hNCs can be maintained after extensive culture expansion.
Methods:
In this study, 2 dimensional (2D) monolayer cultured hNCs (hNCs-2D) and 3 dimensional (3D) spheroids cultured hNCs (hNCs-3D) were examined for chondrogenic capacity in vitro by PCR and immunofluorescence staining for chondrogenic marker, cell survival during cultured and for cartilage regeneration ability in vivo in a rat osteochondral defect model.
Results:
hNCs-3D showed higher viability and more uniform morphology than 3D spheroids cultured hACs (hACs-3D) in culture. hNCs-3D also showed greater expression levels of the chondrocyte-specific marker Type II collagen (COL2A1) and sex-determining region Y (SRY)-box 9 (SOX9) than hNCs-2D. hNCs-3D also expressed chondrogenic markers in collagen. Specially, in the osteochondral defect model, implantation of hNCs-3D led to greater chondrogenic repair of focal cartilage defects in rats than implantation of hNCs-2D.
Conclusion
These data suggest that hNCs-3D are valuable therapeutic agents for repair and regeneration of cartilage defects.
9.Rapid Cartilage Regeneration of Spheroids Composed of Human Nasal Septum-Derived Chondrocyte in Rat Osteochondral Defect Model
Jung Ho JEON ; Byeong Gon YUN ; Min Jae LIM ; Seok Jung KIM ; Mi Hyun LIM ; Jung Yeon LIM ; Sun Hwa PARK ; Sung Won KIM
Tissue Engineering and Regenerative Medicine 2020;17(1):81-90
Background:
Cell-based therapies have been studied for articular cartilage regeneration. Articular cartilage defects have little treatments because articular cartilage was limited regenerative capacity. Damaged articular cartilage is difficult to obtain a successful therapeutic effect. In additionally these articular cartilage defects often cause osteoarthritis. Chondrocyte implantation is a widely available therapy used for regeneration of articular cartilage because this tissue has poor repair capacity after injury. Human nasal septum-drived chondrocytes (hNCs) from the septum show greater proliferation ability and chondrogenic capacity than human articular chondrocytes (hACs), even across different donors with different ages. Moreover, the chondrogenic properties of hNCs can be maintained after extensive culture expansion.
Methods:
In this study, 2 dimensional (2D) monolayer cultured hNCs (hNCs-2D) and 3 dimensional (3D) spheroids cultured hNCs (hNCs-3D) were examined for chondrogenic capacity in vitro by PCR and immunofluorescence staining for chondrogenic marker, cell survival during cultured and for cartilage regeneration ability in vivo in a rat osteochondral defect model.
Results:
hNCs-3D showed higher viability and more uniform morphology than 3D spheroids cultured hACs (hACs-3D) in culture. hNCs-3D also showed greater expression levels of the chondrocyte-specific marker Type II collagen (COL2A1) and sex-determining region Y (SRY)-box 9 (SOX9) than hNCs-2D. hNCs-3D also expressed chondrogenic markers in collagen. Specially, in the osteochondral defect model, implantation of hNCs-3D led to greater chondrogenic repair of focal cartilage defects in rats than implantation of hNCs-2D.
Conclusion
These data suggest that hNCs-3D are valuable therapeutic agents for repair and regeneration of cartilage defects.
10.Changes in the Quality of Life in Patients with Type 2 Diabetes Mellitus According to Physician and Patient Behaviors
Young Joo KIM ; In Kyung JEONG ; Sin Gon KIM ; Dong Hyeok CHO ; Chong Hwa KIM ; Chul Sik KIM ; Won Young LEE ; Kyu Chang WON ; Jin Hye CHA ; Juneyoung LEE ; Doo Man KIM
Diabetes & Metabolism Journal 2020;44(1):91-102
BACKGROUND:
Diabetes mellitus (DM) is the most common chronic metabolic disorder with an increasing prevalence worldwide. According to a previous study, physicians' treatment patterns or patients' behaviors change when they become aware of the risk for cardiovascular (CV) disease in patients with DM. However, there exist controversial reports from previous studies in the impact of physicians' behaviors on the patients' quality of life (QoL) improvements. So we investigate the changes in QoL according to physicians and patients' behavioral changes after the awareness of CV risks in patients with type 2 DM.
METHODS:
Data were obtained from a prospective, observational study where 799 patients aged ≥40 years with type 2 DM were recruited at 24 tertiary hospitals in Korea. Changes in physicians' behaviors were defined as changes in the dose/type of antihypertensive, lipid-lowering, and anti-platelet therapies within 6-month after the awareness of CV risks in patients. Changes in patients' behaviors were based on lifestyle modifications. Audit of Diabetes Dependent Quality of Life comprising 19-life-domains was used.
RESULTS:
The weighted impact score change for local or long-distance journey (P=0.0049), holidays (P=0.0364), and physical health (P=0.0451) domains significantly differed between the two groups; patients whose physician's behaviors changed showed greater improvement than those whose physician's behaviors did not change.
CONCLUSION
This study demonstrates that changes in physicians' behaviors, as a result of perceiving CV risks, improve QoL in some domains of life in DM patients. Physicians should recognize the importance of understanding CV risks and implement appropriate management.

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